Fatores associados a qualidade de vida no trabalho de profissionais da saúde da atenção primária à saúde / Factors associated with the quality of life at work of health professionals in primary health care / Factores asociados a la calidad de vida en el trabajo de los profesionales de la salud en la atención primaria de salud

Objetivo: analisar os principais fatores que estão associados a qualidade de vida no trabalho de profissionais da saúde da atenção primária à saúde. Método: Estudo transversal de abordagem quantitativa, realizada com 163 trabalhadores, os quais respon- deram ao questionário Total Quality of Work Life-42 e a um outro sobre características sociodemográficas e laborais. Resultados: Dos respondentes 84% sexo feminino; 47,9% pardos; 55,2% casados; 55,8% com grau de escolaridade médio, 23,9% graduados e 15,5% possuíam pós-graduação. A renda foi observada correlação positiva entre renda e qualidade de vida, além de fatores pessoais como ser do sexo masculino, solteiro, tempo de trabalho no município (anos). Verificou-se que profissionais do sexo feminino apre- sentaram menores escores de qualidade de vida no aspecto econômico e político quando comparados aos do sexo masculino. Conclusão: Medidas devem ser tomadas para pro- mover um ambiente laboral que mantenha a qualidade de vida no trabalho e, por sua vez, favorecer a saúde física e mental dos profissionais de atenção primária à saúde.

Objective: to analyze the main factors that are associated with the quality of life at work of health professionals in primary health care. Method: Cross-sectional study with a quantitative approach, carried out with 163 workers, who answered the Total Quality of Work Life-42 questionnaire and another on sociodemographic and labor characteristics. Results: Of the respondents, 84% were female; 47.9% brown; 55.2% married; 55.8% had a high school education, 23.9% graduated and 15.5% had a postgraduate degree. Income was observed to have a positive correlation between income and quality of life, in addition to personal factors such as being male, single, working time in the municipality (years). It was found that female professionals had lower quality of life scores in the economic and political aspects when compared to males. Conclusion: Measures must be taken to promote a work environment that maintains the quality of life at work and, in turn, favors the physical and mental health of primary health care professionals.

Objetivo: analizar los principales factores que se asocian a la calidad de vida en el trabajo de los profesionales de la salud en la atención primaria de salud. Método: Estudio transversal con enfoque cuantitativo, realizado con 163 trabajadores, quienes respondieron el cuestionario de Total Quality of Work Life-42 y otro sobre características sociodemográficas y laborales. Resultados: De los encuestados, el 84% eran mujeres; 47,9% marrón; 55,2% casados; El 55,8% tenía educación secundaria, el 23,9% se graduó y el 15,5% tenía posgrado. Ingreso, se observó una correlación positiva entre ingreso y calidad de vida, además de factores personales como ser hombre, soltero, tiempo de trabajo en la ciudad (años). Se constató que las mujeres profesionales tenían puntajes de calidad de vida más bajos en los aspectos económico y político en comparación con los hombres. Conclusión: Se deben tomar medidas para promover un ambiente de trabajo que mantenga la calidad de vida en el trabajo y, a su vez, favorezca la salud física y mental de los profesionales de la atención primaria de salud.

Effects of an extended flexible regimen of an oral contraceptive pill containing 20 µg ethinylestradiol and 3 mg drospirenone on menstrual-related symptoms: a randomised controlled trial.

OBJECTIVES: The aim of the study was to assess the efficacy for menstrual-related symptoms of an extended flexible regimen of an oral contraceptive pill containing 20 µg ethinylestradiol and 3 mg drospirenone in comparison with a 24/4 d cyclical regimen of the same formulation. METHODS: This randomised, non-inferiority, open-label, multicentre study was conducted in women aged 18-39 years. Their menstrual-related symptoms were assessed using the Penn Daily Symptom Rating (DSR17). Participants were randomised to use an extended flexible regimen of 20 µg ethinylestradiol and 3 mg drospirenone (EE/DRSPe.flex), comprising 168 consecutive days with a 4-d hormone-free interval (HFI, allowing for management of unexpected bleeding) or a conventional 24/4 cyclical regimen of the same pill (EE/DRSP24/4). The primary measure of efficacy was the percentage change in DSR17 total score from baseline to cycle 6. The secondary measures of efficacy were the percentage changes in DSR17 total score from baseline after each 28-d interval throughout the entire study and in the scores for individual DSR17 symptoms. RESULTS: The primary analysis demonstrated that EE/DRSPe.flex was not inferior to EE/DRSP24/4 (Mean DSR17 score 9.1; 95% confidence interval (CI) - 2.5, 20.6; p = 0.123). Analysis at intervals throughout the entire evaluation period showed greater reduction in DSR17 total score for EE/DRSPe.flex than for the 24/4 regimen (p < 0.001). The decreases in individual scores for the symptoms 'poor coordination' and 'depression/feeling sad/down or blue' were greater for the extended flexible regimen than for the cyclical regimen (p < 0.05). CONCLUSION: The extended flexible regimen was not inferior to the 24/4 cyclical regimen in terms of the primary endpoint. It significantly improved symptoms in the interval analysis, and the effects on specific DSR17 symptoms, compared with the cyclical regimen.

The effect of pycnogenol on patients with dysmenorrhea using low-dose oral contraceptives.

OBJECTIVE: Menstrual symptoms such as dysmenorrhea usually occur during the hormone-free interval in oral contraceptive users. Progestin withdrawal activates NF-κB transcription factor, which upregulates both vascular endothelial growth factor (VEGF) and Cox-2 expression in the endometrium. The use of natural NF-κB inhibitors such as pycnogenol may block this response, improving dysmenorrhea. PATIENTS AND METHODS: Twenty-four patients with severe dysmenorrhea were allocated to one of two treatment groups. In Group A (n=13), women were treated with an oral contraceptive containing 15 µg of ethinyl estradiol and 60 mg of gestodene (Adoless(®)) in a 24/4 regimen for three consecutive cycles. Women in Group B (n=11) used the same contraceptive regimen together with 100 mg of pycnogenol (Flebon(®)) continuously for 3 months. Pain scores were graded using a visual analog scale (VAS) before and during the hormone-free interval at the end of the third treatment cycle. RESULTS: Before treatment, VAS pain scores for dysmenorrhea were 8 and 9 in Groups A and B, respectively. However, by the end of the third treatment cycle, pain scores had decreased significantly (P<0.05) both in groups A and B. The final pain scores were 6 in Group A and 2 in Group B, a difference that was statistically significant (P<0.0001). In Group B, 27% of the patients became pain-free, while in Group A, none of the women reported complete disappearance of this symptom. The number of bleeding days was also lower in Group B. DISCUSSION: Pycnogenol effectively decreased pain scores and the number of bleeding days when administered concomitantly with a low-dose 24/4 oral contraceptive containing gestodene.

The effect of oral contraceptives on aromatase and Cox-2 expression in the endometrium of patients with idiopathic menorrhagia or adenomyosis.

BACKGROUND: The presence of aromatase and cyclooxygenase-2 (Cox-2) expression was investigated in the endometrium of patients with idiopathic menorrhagia or adenomyosis. The effect of oral contraceptives administered in extended regimens on the endometrial expression of these enzymes was also investigated. METHODS AND RESULTS: Aromatase expression was detected by immunohistochemistry in the endometrial glands and stroma of patients with idiopathic menorrhagia or adenomyosis. There was no difference in the percentage of aromatase expression in the endometria between the two groups. The mean intensity of Cox-2 expression in the glandular epithelium also did not differ significantly between the groups. Among the patients using oral contraceptives in extended regimens, the relative decrease in both aromatase and Cox-2 expression was significantly greater in amenorrheic patients compared with those who were experiencing breakthrough bleeding. CONCLUSION: The presence of aromatase expression in the endometrium is associated with the occurrence of menorrhagia, irrespective of the presence of adenomyosis. Continuous expression of these enzymes in the endometrium of users of oral contraceptives in extended regimens is positively associated with the presence of breakthrough bleeding. This suggests a role for both aromatase and Cox-2 in the etiology of abnormal uterine bleeding.

Combining oral contraceptives with a natural nuclear factor-kappa B inhibitor for the treatment of endometriosis-related pain.

Endometriosis is a chronic disease in which a persistent state of heightened inflammation is maintained by nuclear factor-kappa B (NF-κB) activation. The progestins present in oral contraceptives are potent inhibitors of NF-κB translocation to cell nuclei, while Pycnogenol® (Pinus pinaster) acts by blocking post-translational events. In this study, the effects of Pycnogenol on pain scores were investigated in patients with endometriosis using oral contraceptives containing either gestodene or drospirenone in extended regimens. Pain scores were determined using a visual analog scale before and after 3 months of treatment. Oral contraceptives, used alone (groups 1 and 3) or in association with Pycnogenol (groups 2 and 4), resulted in significant decreases in pain scores after 3 months of treatment; however, this reduction was significantly greater in the groups using oral contraceptives + Pycnogenol (groups 2 and 4) compared with those using oral contraceptives alone (groups 1 and 3). In the groups using oral contraceptives alone, 50% of patients became pain-free by the end of the third month of treatment. These results suggest that Pycnogenol increases the efficacy of oral contraceptives for the treatment of endometriosis-related pain.

Role of inflammation and aromatase expression in the eutopic endometrium and its relationship with the development of endometriosis.

Epigenetic changes favoring the transcription of the aromatase gene in the endometrium allow endometrial cells to survive in ectopic locations by producing estrogens that spare them from destruction through activated macrophages. Local estrogen production hastens prostaglandin synthesis by stimulating COX-2 activity, thus creating a self-perpetuating sequence of augmented estrogen formation and enhanced inflammation. Repetitive retrograde menstruation reintroduces aromatase-positive endometrial cells endowed with the capacity to implant and invade the peritoneum. In order to control endometriosis, an effective medication must inhibit aromatase, block COX-2, decrease fibrosis and induce amenorrhea. Within this framework, progestins, either alone or in the form of oral contraceptives, appear as first-line treatment for endometriosis owing to their capacity to block enzymes such as aromatase and COX-2.

Advantages of the association of resveratrol with oral contraceptives for management of endometriosis-related pain.

BACKGROUND: The effect of resveratrol on the management of endometriosis-related pain was investigated in 12 patients who failed to obtain pain relief during use of an oral contraceptive containing drospirenone + ethinylestradiol. METHODS AND RESULTS: The addition of 30 mg of resveratrol to the contraceptive regimen resulted in a significant reduction in pain scores, with 82% of patients reporting complete resolution of dysmenorrhea and pelvic pain after 2 months of use. In a separate experiment, aromatase and cyclo-oxygenase-2 expression were investigated in the endometrial tissue of 42 patients submitted to laparoscopy and hysteroscopy for the management of endometriosis. Sixteen of these patients were using oral contraceptives alone prior to hospital admission, while the remaining 26 were using them in combination with resveratrol. Inhibition of both aromatase and cyclo-oxygenase-2 expression was significantly greater in the eutopic endometrium of patients using combined drospirenone + resveratrol therapy compared with the endometrium of patients using oral contraceptives alone. CONCLUSION: These results suggest that resveratrol potentiates the effect of oral contraceptives in the management of endometriosis-associated dysmenorrhea by further decreasing aromatase and cyclo-oxygenase-2 expression in the endometrium.

Effect of a hormone-releasing intrauterine system (Mirena(®)) on aromatase and Cox-2 expression in patients with adenomyosis submitted or not, to endometrial resection.

OBJECTIVE: To investigate the effect of a levonorgestrel-releasing intrauterine system (Mirena(®)) on aromatase and cyclooxygenase-2 (Cox-2) expression in the endometrium of patients with adenomyosis who were submitted to endometrial resection at the time of insertion, compared to a group not submitted to endometrial resection and a group of controls with adenomyosis not submitted to any previous hormonal treatment. PATIENTS AND METHODS: Patients with adenomyosis (n = 89) were included in this study. Twenty- two patients had been using Mirena(®) for 5 years but had not been submitted to endometrial resection prior to insertion of the device. Twenty-four patients were submitted to endometrial resection at the time of Mirena(®) insertion. The remaining 43 patients with adenomyosis had undergone no previous hormonal treatment and served as a control group. Cox-2 and aromatase expression were determined in the endometrium by immunohistochemistry. RESULTS: Use of Mirena(®) for 5 years reduced aromatase expression in the endometrium; however, this reduction was significantly greater in the uteri previously submitted to endometrial resection. The reduction in Cox-2 expression was significant only in the uteri submitted to endometrial resection followed by the insertion of Mirena(®). CONCLUSION: Endometrial resection followed by the insertion of Mirena(®) was associated with greater rates of amenorrhea in patients with adenomyosis, which in turn were associated with a more effective inhibition of aromatase and Cox-2 expression in the endometrium.

Correlation between aromatase expression in the eutopic endometrium of symptomatic patients and the presence of endometriosis.

OBJECTIVE: To investigate whether aromatase expression in the eutopic endometrium correlates with the presence and severity of endometriosis in patients with infertility and/or dysmenorrhea undergoing laparoscopy and hysteroscopy. PATIENTS: The study involved 106 patients of reproductive age with symptoms of dysmenorrhea and infertility. Sixteen endometriosis-free asymptomatic patients were used as a control group. METHODS: Concomitant laparoscopy and hysteroscopy was carried out in all cases. An endometrial biopsy was taken to determine aromatase p450 expression by immunohistochemistry. Endometriosis was staged according to the American Society of Reproductive Medicine classification. RESULTS: Endometriosis was diagnosed by laparoscopy in 92/106 symptomatic patients. In this group, aromatase expression was detected in the eutopic endometrium of 66/92 patients with endometriosis (72%) and in 13/14 (95%) patients in the symptomatic, endometriosis-free group (P = 0.09). Aromatase expression was not detected in any patients from the control group. In the endometriosis group, aromatase expression was detected in the eutopic endometrium of 28/45 patients (62%) with American Society of Reproductive Medicine classification stage 1 of the disease, in 11/14 patients (78%) with stage II, 14/20 patients (70%) with stage III, and in 12/13 patients (92%) with stage IV; however, the difference was only statistically significant between stages I and IV (P = 0.04). CONCLUSION: Aromatase expression in the endometrium was associated with the presence of dysmenorrhea and infertility irrespective of the presence of endometriosis. When endometriosis was present, however, there was a tendency for aromatase expression to be positively correlated with dysmenorrhea severity.

Bilateral and simultaneous cystoid macular edema associated with latanoprost use: report of two cases.

Cystoid macular edema is an uncommon, but well known, side effect of latanoprost. Two cases of bilateral and simultaneous cystoid macular edema associated with latanoprost use are described, which complete resolution of the edema is observed upon drug discontinuation.

Bilateral and simultaneous cystoid macular edema associated with latanoprost use: report of two cases / Edema macular cistóide bilateral e simultâneo associado com o uso de latanoprost: relato de dois casos

Cystoid macular edema is an uncommon, but well known, side effect of latanoprost. Two cases of bilateral and simultaneous cystoid macular edema associated with latanoprost use are described, which complete resolution of the edema is observed upon drug discontinuation.

O edema macular cistóide é um efeito colateral incomum, porém bem conhecido, do latanoprost. São descritos dois casos de edema macular cistóide bilateral e simultâneo associado ao uso de latanoprost, em que foi observada completa resolução do edema após a suspensão da droga.

Treinamento aeróbio em natação melhora a resposta de parâmetros metabólicos de ratos durante teste de esforço / Aerobic swimming training improves metabolic parameters response during exertion test in rats

Foram investigados os efeitos do treinamento aeróbio em natação com baixa intensidade sobre as respostas do lactato e da glicose sanguíneos de ratos durante teste de esforço. Ratos Wistar adultos foram distribuídos aleatoriamente em dois grupos: sedentário (n = 6) e treinado (n = 6). Todos receberam água e ração ad libitum e foram mantidos em ambiente com temperatura de 22 ± 2ºC e ciclo claro/escuro de 12 horas. O grupo treinado foi submetido a um programa de natação contínua sem sobrecarga, 30 min/dia, cinco dias/semana, por seis semanas. Três dias após a última sessão de treino, as concentrações sanguíneas de lactato e glicose foram medidas em três momentos durante dois testes de esforço de 20 minutos (repouso, 10 min e 20 min), sendo um sem carga e outro com carga (5 por cento do peso corporal), separados por dois dias. Observou-se correlação inversa entre lactato e glicose durante o exercício (ρ = - 0,74; P < 0,001). A concentração de lactato elevou-se do repouso para 10 min (P < 0,05) e estabilizou-se entre 10 e 20 min, em ambos os grupos nos dois testes. No teste com carga, o lactato estabilizou-se em níveis mais elevados frente aos níveis sem carga (P < 0,05), nos dois grupos. Os animais treinados exibiram níveis de lactato mais baixos do que os sedentários (P < 0,05) nos dois testes. A glicose sanguínea decaiu do repouso até 20 min nos sedentários, no teste com carga (P < 0,05). Nos treinados, a glicose sanguínea estabilizou-se em ambos os testes (P > 0,05). Conclui-se que o treinamento aeróbio em natação aplicado foi capaz de alterar as respostas do lactato e glicose sanguíneos de ratos durante os testes de esforço.

The effects of low intensity aerobic swimming training on blood lactate and glucose responses in rats were investigated during exertion test. Twelve adult male Wistar rats were randomly divided into two groups: sedentary (n= 6) and trained (n= 6). All animals received water and food ad libitum and were kept in a room with temperature of 22 ± 2ºC and dark/light cycle of 12 hours. Animals from trained group were submitted to a swimming training protocol of 30 min/day, 5 days/week, for 6 weeks. Sedentary animals did not exercise. Three days after the last training session all animals were submitted to two 20-minute swimming tests with 48 hour-interval, being one unloaded and the other with a load of 5 percent of body weight. Blood lactate and glucose were measured at rest, 10 min and 20 min of exercise. Negative correlation between blood lactate and glucose levels was observed during the exertion tests (ρ = - 0.74, P<0.001). Blood lactate concentration increased from rest to 10 min of exercise and stabilized from 10 to 20 min of exercise in both exercised and sedentary animals (P<0.05) during the unloaded exertion test. Blood lactate stabilized at higher levels when compared to those in the unloaded test in both groups (P<0.05) during the loaded exertion test. Trained rats presented lower levels of blood lactate than sedentary animals in both exercise tests (P<0.05). Blood glucose declined from rest to 10 min of exercise in sedentary rats during the loaded test (P<0.05). However, in trained animals blood glucose stabilized in both exercise tests (P>0.05). It was concluded that aerobic swimming training changed blood lactate and glucose response in rats during exertion test.

Bleeding patterns and menstrual-related symptoms with the continuous use of a contraceptive combination of ethinylestradiol and drospirenone: a randomized study.

BACKGROUND: The objective of this study was to compare bleeding patterns of women using a contraceptive combination of 30 mcg ethinylestradiol (EE) and 3 mg drospirenone (DRSP) continuously or cyclically. Menstrual-related symptoms were also evaluated. STUDY DESIGN: This open, prospective, randomized study evaluated 78 women using the EE/DRSP combination continuously for 168 days or for six 28-day cycles, each followed by a 7-day hormone-free interval. A diary with pre-established scales was used to assess the frequency and intensity of bleeding and menstrual-related symptoms. RESULTS: Amenorrhea increased with continuous use; 62.2% of women with continuous use were amenorrheic at the end of treatment (95% CI: 46.6-77.8%). Dysmenorrhea, headache, acne, nausea, edema and increased appetite improved significantly in the continuous-use group, and mastalgia and edema in the cyclic-use group (p<.05). Six subjects in the continuous-use group (15.4%) and three in the cyclic-use group (7.7%) discontinued due to adverse events. CONCLUSIONS: Continuous use was associated with amenorrhea and fewer menstrual-related symptoms compared to cyclic use.

Macular edema in multiple evanescent white dot syndrome / Edema macular na síndrome dos múltiplos pontos brancos evanescentes

Eletroretinographic findings show that the transient decreased vision seen in patients with the multiple evanescent white dot syndrome (MEWDS) is related to metabolic disturbances at the level of the retinal pigment epithelium and photoreceptor complex. In this paper, we present a patient with a typical picture of MEWDS associated to macular edema, which could also be a factor to reduce vision in this disorder. Case report of a 53-year-old woman complaining about unilateral decreased vision of 7 days' duration was sent to our retina clinic. A complete ophthalmic examination was performed as well as fluorescein angiography, indocyanine green angiography, Goldmann visual fields and optical coherence tomography (OCT). Best-corrected visual acuity was 20/40 and 20/20, in the right and left eye respectively. Ophthalmoscopy of the affected eye revealed multiple focal outer retinal gray lesions in the perimacular and peripapillary region. There were several orange puntate lesions in the foveolar region. Fluorescein angiography disclosed faint multiple foci of staining in the perimacular and peripapillary area, and some staining of the optic disc. A discrete hyperfluorescence was also observed in the foveal region. OCT disclosed an increase in foveal thickness (231 µm), approximately 25 percent thicker than the opposite normal eye (186 µm). Within 3 months her visual acuity had returned to 20/20 and the foveal thickness returned to a normal value (189 ìm). Although the mechanism of transitory blurred vision is not completely elucidated in cases of MEWDS, we suggest that macular edema may play a role.

PRPÓSITO: Achados eletroretinográficos revelam que a baixa visual transitória observada em pacientes com a síndrome dos múltiplos e evanescentes pontos brancos na retina (MEWDS) está relacionada a distúrbios metabólicos ao nível do epitélio pigmentado da retina e dos fotorreceptores. No presente artigo, nós apresentamos um paciente com um quadro típico de MEWDS associado a edema macular, o qual pode ser um fator que reduz a acuidade visual. : Relato de caso. Sexo feminino, 53 anos, queixando-se de baixa visual há 7 dias foi encaminhada ao Setor de Retina. Realizado exame oftalmológico completo, que incluiu: angiofluoresceinografia, angiografia com indocianina verde, campo visual de Goldmann e tomografia de coerência óptica (OCT). RESULTADOS: A acuidade visual era de 20/20 e 20/40 nos olhos direito e esquerdo, respectivamente. A oftalmoscopia do olho afetado revelou lesões acinzentadas, múltiplas, profundas, nas regiões perimaculares e peridiscais. A mácula tinha aspecto granulado. A angiografia fluoresceínica revelou hiperfluorescência gradativa das lesões, bem como do nervo óptico. O OCT revelou um aumento da espessura foveal no olho afetado (231µm), aproximadamente 25 por cento maior que a espessura do olho normal contralateral (186µm). Após 3 meses de evolução sem tratamento, a acuidade visual retornou a 20/20 e a espessura foveal já era normal (189 µm). CONCLUSÃO: Embora o mecanismo de baixa visual transitória não esteja completamente elucidada em MEWDS, nós sugerimos que o edema macular possa ser uma das causas.

Effect of a continuous regimen of contraceptive combination of ethinylestradiol and drospirenone on lipid, carbohydrate and coagulation profiles.

BACKGROUND: The objective of this study was to evaluate the effects of a contraceptive pill containing ethinylestradiol (30 mcg) and drospirenone (3 mg) in a continuous regimen on lipid, carbohydrate and coagulation parameters. STUDY DESIGN: This open, prospective, randomized study included 78 participants (mean age 27.8 years) who were randomized into two groups to use the pill continuously for 168 days or for six 28-day cycles with a 7-day hormone-free interval between cycles. Markers of lipid, carbohydrate and coagulation profiles were measured prior to initiation and after the 6 months of pill use. RESULTS: No statistically significant differences were found between the two contraceptive regimens with respect to carbohydrate or lipid profiles or in the parameters related to coagulation. CONCLUSIONS: The contraceptive combination of ethinylestradiol and drospirenone used in a continuous regimen was associated with metabolic alterations similar to those found during the traditional cyclic regimen of oral contraceptive use.

The effect of a continuous regimen of drospirenone 3 mg/ethinylestradiol 30 microg on Cox-2 and Ki-67 expression in the endometrium.

OBJECTIVE: To study Cox-2 expression in relation to bleeding patterns in patients using an oral contraceptive containing 3 mg of drospirenone and 30 microg of ethinylestradiol (DRSP/EE). METHODS: Forty-three patients of reproductive age with symptoms of menorrhagia and dysmenorrhoea, who were submitted to endometrial resection, were enrolled. Twelve patients were in the proliferative phase and the remaining 31 were either currently using DRSP/EE or had discontinued its use four to eight days prior to hysteroscopy. Cox-2 and Ki-67 expression were determined in the endometrium using immunohistochemistry. RESULTS: Cox-2 expression was significantly inhibited in the glandular epithelium of patients who became amenorrhoeic during DRSP/EE use; however, in patients with breakthrough bleeding and in those who had stopped oral contraceptive use, a significant increase occurred in Cox-2 expression in the endometrium. Ki-67 expression decreased significantly during DRSP/EE use, but returned to proliferative phase values four to eight days after discontinuation of treatment. CONCLUSION: These results suggest that endometrial bleeding during DRSP/EE use is associated with an increase in Cox-2 expression in the endometrium. A similar increase was also seen four to eight days following discontinuation of the oral contraceptive.

Activation of NF-kappaB and COX-2 expression is associated with breakthrough bleeding in patients using oral contraceptives in extended regimens.

The objective of the present study was to determine whether there is an increase in endometrial inflammation associated with the occurrence of breakthrough bleeding in patients using an oral contraceptive in extended regimens. The presence of nuclear factor NF-kappaB and Cox-2 expression was determined by immunohistochemistry in endometrial samples removed by hysteroscopy from patients with breakthrough bleeding during continuous use of an oral contraceptive containing gestodene. All patients had a history of menorrhagia associated or not with the presence of uterine pathology. The percentage of endometria showing a positive staining reaction for NF-kappaB in cell nuclei was significantly higher in patients with breakthrough bleeding than in those with amenorrhea. Cox-2 expression in the endometrium was also significantly more frequent in patients with breakthrough bleeding. The occurrence of breakthrough bleeding in patients with uterine pathology using combined oral contraceptives is associated with the activation of endometrial inflammation through the NF-kappaB pathway.

Is aromatase expression in the endometrium the cause of endometriosis and related infertility?

Aromatase expression in the endometrium seems to play a pivotal role in the development of endometriotic lesions. Because inflammatory mediators such as prostaglandin E2 appear to activate aromatase in the cells of the endometrial stroma, it was hypothesised that the ensuing inflammation caused by the arrival of aromatase-positive cells in the peritoneal cavity would stimulate local estrogen production, which would in turn facilitate the development of endometriotic lesions by suppressing macrophage phagocytosis. Aromatase expression in the eutopic endometrium will also hamper ovum nidation, thus causing infertility. Progestins, such as gestodene and danazol, are potent inhibitors of aromatase expression in the endometrium, and the use of vaginal rings with danazol in doses that do not block ovulation is associated with the occurrence of pregnancy in patients with severe endometriosis without the need for surgery. A local effect on the endometrium suppressing aromatase expression has been suggested as a possible mechanism of action for the danazol ring.

Testosterone replacement therapy in the climacteric: benefits beyond sexuality.

Testosterone therapy during menopause has a wide range of benefits that reach beyond the realm of human sexuality. This is a consequence not only of the widespread distribution of androgen receptors in various extragonadal tissues but also of the conversion of androgens to estrogens in the tissues in which aromatase expression is present. For this reason, testosterone therapy during the climacteric years will not only supply androgens but will also stimulate estrogen production in tissues that express aromatase. Furthermore, the bioavailability of androgens to the tissues depends not only on the rate of their production by the postmenopausal ovaries and adrenals but also on the circulating levels of sex hormone-binding globulin (SHBG). Tibolone inhibits SHBG production in the liver, thus increasing free testosterone levels. The association of tibolone with testosterone as a form of androgen replacement therapy during the climacteric is discussed, as is the use of low-dose testosterone, tibolone or the association of both in perimenopausal patients with signs of androgen deficiency. Testosterone treatment has a boosting effect not only on human sexuality but also on the sensation of well-being, a stimulatory effect conferred by the increase in beta-endorphins.

Effect of oral contraceptives on vascular endothelial growth factor, Cox-2 and aromatase expression in the endometrium of uteri affected by myomas and associated pathologies.

BACKGROUND: The study was conducted to evaluate vascular endothelial growth factor (VEGF), Cox-2 and aromatase expression in the endometrium of uteri with myomas and other associated pathologies. STUDY DESIGN: Hysteroscopy was performed in 118 women of reproductive age with myomas and menorrhagia, 40 of whom were using a pill containing 75 mcg gestodene+30 mcg ethinylestradiol. Aromatase p450, VEGF and Cox-2 expression was detected using immunohistochemistry. Fisher's Exact Test and the Mann-Whitney test were used in the statistical analysis, with significance established at p<.05. RESULTS: In patients with myomas and menorrhagia, associated pathologies such as adenomyosis, endometrial polyps and endometriosis were found in 32%, 12% and 17% of cases, respectively. Aromatase, Cox-2 and VEGF expression was greater during the proliferative phase compared to the luteal phase of the cycle or following oral contraceptive use. CONCLUSION: Endogenous progesterone or combined oral contraceptives are potent inhibitors of VEGF, aromatase and Cox-2 expression in the endometrium of patients with myomas and menorrhagia.